| First Author | Dong MB | Year | 2019 |
| Journal | Cell | Volume | 178 |
| Issue | 5 | Pages | 1189-1204.e23 |
| PubMed ID | 31442407 | Mgi Jnum | J:390702 |
| Mgi Id | MGI:8235894 | Doi | 10.1016/j.cell.2019.07.044 |
| Citation | Dong MB, et al. (2019) Systematic Immunotherapy Target Discovery Using Genome-Scale In Vivo CRISPR Screens in CD8 T Cells. Cell 178(5):1189-1204.e23 |
| abstractText | CD8 T cells play essential roles in anti-tumor immune responses. Here, we performed genome-scale CRISPR screens in CD8 T cells directly under cancer immunotherapy settings and identified regulators of tumor infiltration and degranulation. The in vivo screen robustly re-identified canonical immunotherapy targets such as PD-1 and Tim-3, along with genes that have not been characterized in T cells. The infiltration and degranulation screens converged on an RNA helicase Dhx37. Dhx37 knockout enhanced the efficacy of antigen-specific CD8 T cells against triple-negative breast cancer in vivo. Immunological characterization in mouse and human CD8 T cells revealed that DHX37 suppresses effector functions, cytokine production, and T cell activation. Transcriptomic profiling and biochemical interrogation revealed a role for DHX37 in modulating NF-kappaB. These data demonstrate high-throughput in vivo genetic screens for immunotherapy target discovery and establishes DHX37 as a functional regulator of CD8 T cells. |
